Artificial kidney

ABSTRACT

AN EXTRA-CORPOREAL DEVICE EMPLOYING DIALYSIS AND FILTRATION MEANS PERFORMS THE FUNCTION OF A NATURAL KIDNEY. IN THE DEVICE, A BODILY FLUID SUCH AS PERITIONAL FLUID OR ARTERIAL BLOOD IS WITHDRAWN FROM THE BODY AND PASSED THROUGH A DIALIZER THAT CAUSES SELECTIVE DIFFUSION OF TOXIC, LOW MOLECULAR WEIGHT SOLUTES INTO A WATER-CONTAINING DIALYSATE, THE DIALYSATE AND SOLUTES ARE THEN PASSED THROUGH A FILTRATION MEANS OR COMBINATION OF FILTRATION AND ELECTRODIALZING MEANS THAT PERMIT ONLY THE PASSAGE OF PURE WATER OR PURE WATER DISSOLVED ELECTROLYTES WHILE RETAINING THE LOW MOLECULAR WEIGHT TOXIC SOLUTES. THE PURIFIED FILTRATE FROM THE FILTRATION MEANS IS RECYCLED AND COMBINED WITH A CONTROLLED AMOUNT OF MAKE-UP ELECTROLYTE SOLUTION AS THE DIALYSATE FOR THE DIALYZER AND THE UNFILTERED RESIDUE FROM THE FILTRATION MEANS IS DISCHARGE AS WASTE THE PERITONEAL FLUID OR BLOOD IN TRANSIT THROUGH THE DIALYZER IS THUS CLEANED OF TOXIC SUBSTANCES AND IS SUITABLE FOR RETURN.

March 26, 1974 c] 5, BROWN 3,799,813

ARTIFICIAL KIDNEY Filed July 9, 1971 4 Shah-Shut 1 METERING PUMPS VENOUSRETURN) as A3 RESERVOIR FOR CANNULA CONCENTRATED Q95 MAKE-UP ELECTRO l80 LYTE SOLUTION I I93) l1 ::::::TQ l4 POWER J M SOURCE I82 "I? L 82 ICANNULA Ii 6 2| 1A S E SSURE Q I53 RELIEF VALVE MAKE-UP ELECTROLYTES 893 I/VENOUS RETURN I CANNULA U METERING j PUMP fig 2| ARTERIAL BLOOD 6 9I CANNUL" Q'BE E -K"- iL IE ig Is 1.76 15 v KELECTRODIALYSIS URINALI 93MAKE-UP ELECTROLYTES VENOUS RETURN 94 i CANNULA 0 /METER|NG PUMP I?HYPER- HEMO CANNULA DIALYZER FILTER IO ARTERIAI. I2 J 6 O BLOOD T Ej 2|I5 ELECTRO- E: F/G l6 DIALYSIS URINE PUMP INVENTOR CLINTON E. BROWNATTORNEYS March 26, 197 c. E. BROWN ARTIFICIAL KIDNEY '4 Shani-Shoot 2MAKE-UP ELECTROLYTES Filed July 9, 1971 HYPER- FILTER METERING PUMPWATER a ELECTRO LYTES PERMEABLE HIGH PRESSURE MEMBRANE HEMO DIALYSISVENOUS RETURN CANNULA CANNULA WARTERIAL BLOOD FIG. 10

'PUMP To URINAL INVENTOR CLINTON E. BROWN 1m fndmok 752C260 9(QATTORNEY? CONCENTRATE OUTLET SPENT DIALYSATE INLET MEMBRANE TUBEBUNDLE SPENT DIALYSATE B March 26, 1974 c. E. BROWN ARTIFICIAL KIDNEYFiled July 9, 1971 Zimegan, J%7Q 5ZSOIZ QFaZafiow ATTORNEYS March 26,1974 c. E. BROWN ARTIFICIAL KIDNEY 4. shun-Sum ARTERIAL BLOOD MAKE- UPELECTROLYTES CANNULA VENOUS RETURN Filed July 9,

FROM \YARTERIAL TO VENOUS CANNULA I mvswon CLINTON E. BROWN ATTORNEYSUnited States Patent 3,799,873 ARTIFICIAL KIDNEY Clinton E. Brown,Silver Spring, Md., assig'nor to Hydronautics, Incorporated, Laurel, Md.

Continuation-impart of abandoned application Ser. No.

3,102, Jan. 15, 1970, which is a continuation-in-part of applicationSer. No. 722,727, Apr. 19, 1968, now

Patent No. 3,579,441. This application July 9, 1971,

Ser. No. 161,864

Int. Cl. B01d 13/00 US. Cl. 210-22 25 Claims ABSTRACT OF THE DISCLOSUREAn extra-corporeal device employing dialysis and filtration meansperforms the function of a natural kidney. In the device, a bodily fluidsuch as peritoneal fluid or arterial blood is withdrawn from the bodyand passed through a dializer that causes selective diffusion of toxic,low molecular weight solutes into a water-containing dialysate. Thedialysate and solutes are then passed through a filtration means orcombination of filtration and electrodialzing means that permit only thepassage of pure water or pure water and dissolved electrolytes whileretaining the low molecular weight toxic solutes. The purified filtratefrom the filtration means is recycled and combined with a controlledamount of make-up electrolyte solution as the dialysate for the dialyzerand the unfiltered residue from the filtration means is discharged aswaste. The peritoneal fluid or blood in transit through the dialyzer isthus cleansed of toxic substances and is suitable for return.

This application is a continuation-in-part of my copending applicationSer. No. 3,102, filed Jan. 15, 1970, now abandoned, which is acontinuation-in-part of application Ser. No. 722,727, filed Apr. 19,1968, now US. Pat. No. 3,579,441.

This invention relates to artificial kidneys for removing toxicsubstances from bodily fluids, such as blood or peritoneal fluid. Inrecent years the use of such devices has prolonged the lives of humanbeings with damaged or inoperative kidneys. The physiology of the humankidney is fairly well understood and involves the removal of nonvolatilewastes from the bloodstream and the continuous regulation of the bloodcomposition such that the conditions in body tissues necessary for thelife of cells are maintained. Accordingly, when the kidneys are notoperating properly, these functions must be performed by some artificialmeans, lest conditions of uremia and eelctrolyte imbalance develop. Oncethese conditions exist, the bloodstream becomes increasingly toxic.

Artificial kidneys have been developed which, when used for severalhours several times per week are capable of reducing the level ofconcentration of toxic substances in the blood. A wash solution,carefully formulated so as to be isotonic to blood, is introduced intothese devices such that certain desirable constituents of the blood,e.g., electrolytes, are not lost.

It can be seen that the use of these prior art devices raises severalserious problems. First, a high volume of reconstituting or washsolution is required. This large amount of liquid is generally suppliedfrom a bulky and immobile reservoir. Second, prior art devices are useddiscontinuously. Periods of dialysis shorter than six (6) hours twice aweek appear to be ineffective, and during the dialysis period thepatient is immobile. Another undesirable but inavoidable effect ofdiscontinuous use is a periodic buildup and withdrawal of wastes. Justbefore the use of a prior art artificial kidney, the concentration ofvarious solutes in the patients bloodstream is abnor-'* mally high, andjust after treatment the concentration P ICC throughout the body may notbe in equilibrium with its inherent undesirable effects. Third, theknown devices are expensive to use and require the assistance of trainedpersonnel.

In my US. Pat. No. 3,579,441, many of the problems of prior artartificial kidneys were basically solved. In this patent, there isdescribed a device employing a plurality of filtration means thatperform in combination the functions of a normal kidney. Arterial bloodis first filtered through a plurality of highly selectiveultrafiltration membranes that are designed to retain macromolceularweight blood constituents while permitting the passage of water and thelow molecular weight toxic solutes in the blood. The filtrate containingthe water and solutes is then passed through a plurality of even finer,hyperfiltration membranes that permit only the passage of pure water asfiltrate while retaining the toxic solutes on the membranes. The solutesretained by the hyperfilters are discharged as waste and the purifiedfiltrate consisting essentially of pure water or pure water andelectrolytes is mixed with the macromolecular weight blood constituentsretained by the ultrafilter to form the venous return. Since somequantities of desirable electrolytes are lost during filtration, acontrolled amount of make-up electrolyte solution generally must beadded to the purified filtrate to bring it to an isotonic condition.

While the use of this novel combination of filtration means represents asignificant improvement over the art by providing both an effective andcontinuous artificial kidney that can be conveniently worn on the body,the device still faces some problems. The previous use of selectivefiltration means, for example, that permitted passage of low molecularweight solutes while retaining high molecular weight substances,resulted in some clogging of the membranes, especially at the highfiltration rates necessary for the device to operate effectively. Whilethis could be avoided by decreasing filtration rates, the efliciency ofthe device was, of course, also decreased. Further, a large surfacearea, and generally on the order of about 2,000 square centimeters, wasnecessary in the ultrafiltration means to achieve effective andefficient filtrate rates.

The necessity of periodically adding make-up electrolyte solution to thepurified filtrate that was returned and mixed with the macromolecularconstituents, was a source of contamination to the blood, and the waterused in the preparation of this solution had to be carefully treated tobe sure it was sterile and pyrogen free.

In accordance with one embodiment of the present invention, it has beenfound that the foregoing disadvantages can be substantially eliminatedand the device described in my copending application improved byreplacing the ultrafiltration means with a hemodialysis means. Thus,instead of cleansing the blood by passing it through a filtration meansas in my previous device, the blood is cleansed by drawing the toxicsubstances across a dialysis membrane.

In a hemodialyzer, a carefully formulated dialysate, containing waterand a certain concentration of electrolytes, is passed along one side ofthe membranes in countercurrent flow to the flow of the blood on theopposite side of the membranes to cause selective diffusion of theundesirable toxic substances across the membranes and into thedialysate. The dialysate preferably contains a concentration ofelectrolytes and water similar to that of the blood to prevent theircross diffusion during hemodialysis.

Thus, the cleansed blood, not depleted of its primary water content,electrolytes or other desirable constituents as occurred previouslyduring ultrafiltration, is immediately suitable for venous return. Thespent dialysate is recovered and purified of the toxic substances withthe same hyperfiltration means utilized in my previous device andrecycled as reconstituted dialysate to the hemodlalyzer to provide acompact, mobile device that can be continuously and conveniently worn bythe user.

In the present device, the dialysate, containing makeup electrolytes,travels in a closed circuit, independent of the blood circuit, thuseliminating a previous source of blood contamination when make-upelectrolyte solution was added directly to venous return.

Further, and because the blood is cleansed by diffusion of toxicsubstances out of the blood and not by filtration by passing thesubstances through filters as solutes in the bloods water content, thehigh filtration rates and the large surface area previously required aresubstantially reduced, thereby further enhancing the efi'iciency in boththe size and operation of the present device.

In accordance with a further embodiment, the wearable artificial kidneyof this invention may also be used in recirculation peritoneal dialysisin which peritoneal fluid from the peritoneum is withdrawn from the bodyand cleansed of toxic substances such as urea creatinine, uric acid,etc., that have ditfused across the peritoneal membrane from the bloodand into the peritoneal fluid, thereby reducing the concentration ofthese toxic substances in the blood. The body fluid suitable for use inthe kidney of this invention and as used in the specification and claimsis, therefore, intended to include peritoneal fluid as well as arterialblood.

When the kdney is used with peritoneal fluid, the cannulas are insertedinto the peritoneal cavity rather than the arteries and a circulatingpump is used to withdraw the peritoneal fluid and to pass it to thedialysis means of the kidney. When the kidney is used with blood, thepump is not necessary because the human heart supplies the pressureneeded to pass the blood to the dialyzer.

As the peritoneal fluid passes through the dialyzer, the dialyzercleanses the peritoneal fluid in the same manner as the blood iscleansed and a make-up solution is similarly added to the dialysatereturning to the dialyzer.

Thus, the artificial kidney of this invention can be used equally wellwith either peritoneal fluid or blood and without any significant changein the construction of the device.

In accordance with a preferred embodiment of this invention, the deviceincludes a dialysis means, a dialysate filtration means, a high'pressurepump, a metering pump, and a small reservoir for make-up electrolytesolution. The combination of these elements forms a compact device whichcan be worn on the body with minimum interference to sleep, freemovement, daily toilet, sexual activity, and so forth.

More particularly and in accordance with the present invention, arterialblood or peritoneal fluid from the peritoneum is drawn ofi and fed toone side of the membranes of the dialysis means. A water-containingdialysate, essentially free of toxic solutes in the blood, is passed incountercurrent flow to the body fluid along the other side of thedialysis membranes to establish a concentration gradient, therebycausing dilfusion of the toxic solutes into the dialysate. Dialysate iscontinually flushed through the dialysis means so that the concentrationof toxic solutes in the dialysate never reaches its equivalent level inthe body fluid being processed and a strong concentration gradient isthereby continuously maintained across the membranes.

The dialysate is carefully formulated to be not only free of toxicsolutes, but to contain substances that are desired to be retained inthe blood at concentration levels approximately equivalent to theirlevel in the blood. Such substances include, for example, glucose,sodium chloride, sodium bicarbonate, potassium, and other desirableelectrolytes. Hence, the dialysate does not establish a concentrationgradient for these substances to prevent their loss from the body fluid.

Spent dialysate containing the toxic solutes is then pumped from thedialyzer to the dialysate filtratlon means, which, preferably, is onlypermeable to water and electrolytes, by the high pressure pump. Thepurpose of the dialysate filtration means is to remove the toxicsolutes, such as urea, uric acid, creatinine, and the like from thespent dialysate. The filtrate thus contains relatively pure water and issuitable for recycle for use in preparing the dialysate for the dialysismeans. The unfiltered residue retained by the filtration means arewastes and are deposited in a small cannister which is periodicallyemptied.

In operation, most of the electrolytes along with some of the water willbe filtered out and rejected along with the wastes. Thus, a small amountof a highly concentrated aqueous solution of electrolytes is fed fromthe make-up electrolyte reservoir and mixed with the purified dialysatefiltrate in the metering pump to provide the necessary reconstituteddialysate for use in the dialysis means. The metering pump supplies apredetermined amount of a highly concentrated aqueous solution of suchelectrolytes as sodium chloride, potassium, sodium bicarbonate, etc., tothe purified dialysate to bring it to an isotonic condition. In mostcases, the bulk of the makeup solution is concentrated saline.

When used with peritoneal fluid, the make-up solution metered into thedialysate for return to the dialyzer should also contain dextrose and/or sorbitol in a concentration of about 1% by weight. The dextrose orsorbitol permeates through the membrane in the dialyzer and into theperitoneal fluid to provide, as is well known to those skilled in theart of peritoneal dialysis, an osmotic induced withdrawal of water fromthe body into the peritoneal fluid. This is required because the kidneyof this invention rejects water and this water is provided byWithdrawing the water from the body into the peritoneal fluid.

The net result of all the elements of the invention working incombination mimics the function of a normal kidney by discardingnitrogenous wastes while retaining plasma, water, and the concentrationof electrolytes in the blood. In some cases, dissolved sugars may belost, but these may be replaced orally.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory but arenot restrictive of this invention.

The accompanying drawings which are incorporated in and constitute apart of the specification, illustrate several embodiments of theinvention, and together with the description serve to explain theprinciples of the invention.

01: the drawings:

FIGS. 1A, 1B, 1C, and ID are schematic representations of the device ofthis invention, in which 1A is the basic embodiment, and LB, 1C, and IDare alternative embodiments, being variations of the basic embodiments;

FIG. 2. is a fragmentary perspective view of the construction details ofthe dialyzer of this invention;

FIG. 3A is a cross-sectional view of a part of the hyperfilter of thisinvention;

FIG. 3B is an exploded perspective view of an alternative embodiment ofthe hyperfilter of this invention;

FIG. 4 is a plan view of the motor, high-pressure pump and metering pumpof this invention;

FIG. 5 is a cross-sectional view taken along line 55 of FIG. 4;

FIG. 6 is a side elevational view of the apparatus of FIG. 4;

FIG. 7 is an enlarged cross-sectional view taken along line 7-7 of FIG.4; and

FIG. 8 is an exploded perspective view of one embodiment of anartificial kidney constructed according to this invention.

Reference will now be made in detail to the present preferredembodiments of the invention, examples of which are illustrated in theaccompanying drawings.

For convenience, the invention will be described as it relates to theprocessing of arterial blood. It is to be understood, however, asdescribed above, that peritoneal fluid from the peritoneal cavity may beused in place of blood in the artificial kidney of this invention.

By peritoneal fluid is meant that fluid naturally existing in theperitoneal cavity, supplemented, if desired, to increase its volume withconventional peritoneal di alysis solutions. For a more thoroughdiscussion of peritoneal dialysis as a means for performing the functionof a natural kidney and particularly recirculation peritoneal dialysis,reference is made to an article by J. H. Shinaberger, L. Shear and K. G.Barry, entitled, increasing Efliciency of Peritoneal Dialysis,Transactions of American Society of Artificial Internal Organs, volume-I'I, pages 76-82, 1965.

With reference to FIGS. 1A and 8, arterial blood is drawn from the bodyby a conventional cannula and forced by the pumping action of the bodysheart into the dialysis means or hemodialyzer 12. Simultaneously, freshdialysate 14 is passed through hemodialyzer 12 in countercurrent flow tothe blood and spent dialysate 16 is drawn off from the hemodialyzer bythe low pressure side of a high pressure pump &1. FIG. 2 shows in moredetail the construction of hemodialyzer 12 and will be discussed in moredetail below.

Spent dialysate 16 is then channeled through pump 81 and forced throughinput line 21 to hyperfilter 60' (60 of FIG. *8) by the high pressureside of the pump. The filtrate 17 emerging from hyperfilter 60 isessentially pure water and electrolytes, while the non-permeatingsolutes are deposited in a detachable urinal 151.

With reference to FIGS. 3A and 3B, the hyperfiltrate 17 from hyperfilter60 is drawn off transversely and continuously to the filter surfaces 63,while the input 21 which is the spent dialysate 16 under pressure,travels through the hyperfilter with a motion parallel to the filteringsurfaces 63 and emerges as a concentrated solution 15 of low molecularweight solutes, such as urea, creatinine, uric acid, and electrolytes.Pressure is maintained at the proper level in hyperfilter 60 by the pump81 and pressure relief valve 153 in the urine rejection line 15. Therelief valve is designed to permit a continuous flow of spent dialysatethrough hyperfilter 60 and a continuous flow of wastes 15 to urinal 151.Due to the high volume of recovered water 17, the volume of waste 15 isof manageable proportions, and the urinal 151 need be detached andemptied only infrequently.

As previously noted, pump 81 provides the pressure across hyperfilter60. The pump and the metering system 93 are driven by A.C. or D.C. motor82 (a DC. motor is preferred when a wearable system is contemplated) andby power pack 182, which preferably comprises rechargeable batteries.The suction side of the metering system 93 draws hyperfiltrate 17 and acontrolled amount of concentrated make-up electrolyte solution 195 fromthe makeup reservoir 193, and forces them into the same efilux line at196 to form a reconstituted dialysate 14 with the desired concentrationof sodium, potassium, bicarbonate, phosphate, chloride and sulfate ionsand the like. for return to hemodialyzer 12. The cleansed whole blood isreturned to the body via the venous cannula 18.

Refer-ring to FIG. 2, the internal construction details of hemodialyzer12 of this invention will become evident. This perspective view isfragmentary in that only two (2) complete arterial blood channels 45 anddialysate channels 53 are shown. In practice, the hemodialyzer of thisinvention contains numerous blood and dialysate channels. The designshown is a laminar arrangement; however, it will be understood thatother arrangements may be used, such as tubules, in which the blood anddialysate flow is countercurrent and parallel to the longitudinal axisof the individual tubules. In either case, the polarization of thesurfaces of the blood channels is negligible when sufiiciently smalldimensions are used.

As seen in FIG. 2, the laminar construction consists of a series ofmembranes 43, a series of porous supports forming dialysate channels 53,and a series of parallel rows of. cylinder-shaped spacers 41, allarranged such that the space between the surfaces of two (2) adjacentmem branes 43 provides a blood channel 45.

Various membranes suitable for hemodialysis and well known to thoseskilled in the art may be used as membrane elements 43. Such membranesinclude: cellophane, cuprophane, polyvinyl alcohol, and celluloseacetate. In selecting the membranes, it is desirable to employ membraneswhich have heparin or other anti-blood clotting agents incorporated inthe membrane. The other materials used in the construction ofhemodialyzer 12 which are in contact with the blood should besubstantially nonthrombogenic, i.e., not tending to produce blood clots.Preferred non-thrombogenic materials are heparinizedpolytetrafluoroethylene, heparinized surgical grade silicone, and thelike. Thus, spacers 41 are preferably polytetrafluoroethylenemono-filaments marketed by the Du Pont Company under the trade namesTeflon TFE, or Teflon FEP; but the porous support material formingdialysate channels 53, since these channels are not directly in contactwith blood, can comprise nylon cloth, or the like.

The preferred thickness of channels 53 is fom about 50 to 150 microns.The blood channels 45 between membranes 43 are preferably as small aspossible, down to about 7 microns which is the size of a red blood cell.Accordingly, channels 45 will range from about 7 microns up to about 100microns.

As the arterial blood passes through blood channels 45 parallel tospacers 41 and countercurrent to the flow of dialysate through dialysatechannels 53, the toxic blood solutes having a molecular weight less than10,000 or so diifuse perpendicularly to the blood flow through membranes43 and into the dialysate channels 53, the spent dialysate 16 containingthe solutes being drawn oif continuously from the opposite end ofhemodialyzer 12. The design described above permits the completehemodialyzer unit to be housed in a rectangular box with dimensions of16 x 6 x 0.8 centimeters. The core of the dialyzer unit beingapproximately 15 x 5 x 0.5 centimeters in volume. The assembled unitweighs approximately 100 grams.

FIG. 3A shows the details of hyperfilter designed similarly to thelaminar assembly of hemodialyzer 12 but functioning as a filtrationsystem rather than a dialysis system. The instant assembly consists of aseries of spaces each designated 65, defined by membranes 63, themembranes being supported by porous plates 67. Between each set ofporous plates 67 is another space 69 from which the hyperfiltrate isdrawn off by the manifold as shown. This hyperfiltrate 17 consistsessentially of pure water or pure water and electrolytes. The inletmanifold 21 allows spent dialysate drawn from hemodialyzer 12 and passedthrough pump 81 to pass into spaces 65. The pure water or water pluselectrolytes passes through membranes 63 into spaces 69 in a directionthat is essentially perpendicular to the flow through spaces 65. Thematerial 15 emerging from spaces and into the outlet manifold is highlyconcentrated and contains wastes such as urea, uric acid, creatinine,etc.

Since hyperfilter 60 is not in contact with the blood, nonthrombogenicmaterials need not be used in its construction. The preferred materialto be used for membranes 63 is cellulose acetate. These membranes areprepared by dissolving the cellulose acetate in acetone and aconditioning agent, generally formamide. This solution is formed intosheets, and after a preliminary short air evaporation, the material isimmersed in cold water, thus removing the acetone and formamide andgelling the cellulose acetate. Subsequently, the film is conditioned byheat treatment at to C. The surfaces of the membranes 63 in contact withthe spaces 65 are under high pressure, In our basic embodiment, weprefer at least 600 p.s.i. The total area of these surfaces may vary,and we prefer an active total membrane surface of approximately 1,000 to3,000 square centimeters.

Again, the membranes of the finished package may be of variousdimensions, and in this connection, we prefer 15 centimeters length byabout centimeters width by about 1 centimeter or less thickness. Thiswould mean that the entire hyperfilter would comprise about 22 membranes63. The spacing 65 should be about 50 to 300 microns.

FIG. 3B illustrates an alternative design 60' for the hyperfilter ofthis invention. The membranes tubes 63' shown in the figure are producedby confining a plug of cellulose acetate solution in acetone in a tubeof appropriate diameter, and blowing the plug by means of a column ofair under pressure. The advancing air column forces the celluloseacetate solution towards the walls of the support tube, forming it intoa thin cylindrical-shaped tube concentric with the supporting wall. Acolumn of water following the air removes the acetone from the mixture,and eoagulates the cellulose acetate into a solid hollow tube. Tubeswith a diameter of less than 500 microns can easily be made. Thepreferred diameter is about 250 microns. Thus, the tubes shown in thedrawing are greatly enlarged for purposes of illustration. The tubesthemselves have little inherent mechanical strength and are supported byporous support tubes, not shown, made from sintered stainless steel,Inconel, silver, tantalum and the like. Nonmetallic materials suitablefor making support tubes are glass fibers stiffened with epoxy orpolyester resin, woven nylon, or glass braid stiffened with resin andfillers, sintered ceramics, and sintered glasses. The tubes should havean outside diameter of about 500 microns, should be microporous, shouldbe able to withstand high internal pressures, and should be inert tobody fluids, both in the sense of being corrosion resistant and in thesense of not releasing toxic substances. Thus, the list of materialsgiven above is not intended to be exhaustive, since any material thatsatisfies these conditions may be used. The tubular type membraneassembly would be similar in volume to the flat plate assembly; aIS-centimeter length, a 1.7 cm. diameter, and an overall weight of about100 to 150 grams can be obtained in practice. Both hyperfilters 60 and60' are designed to reduce polarization to a negligible minimum.

FIGS. 4, 5, 6, and 7 show the details of the preferred embodiment of thenovel high-pressure micro-pump and metering system assembly 81 of thisinvention. The assembly is mounted on a rigid base 100 and includes ashaft 86, which is common to the micro-pump and metering portions of theassembly and a suitable electric motor 82 for driving shaft 86 through asleeve coupling 83, a shaft speed of about 3,600 r.p.m. being preferred.Shaft 86 is supported by two (2) shaft hangers 85 and 85.1 which houseball-bearings 87 and 87.1 and retainer rings 84 and 84.1, respectively.Turning with the shaft 86 is a ball-bearing cam system which convertsthe rotary motion of shaft 86 into reciprocating motion. As shown inFIG. 5, an example of an eccentric drive cam is 89, and an example of aball-bearing for this cam arrangement is 88.

The reciprocating motion from drive cam 89 is transmitted to the piston99 of a pump chamber 90 (see FIG. 5) where a silastic pump diaphragm 91in the chamber is alternately squeezed and released to produce a pumpingaction. A return spring member 92 is provided to return piston 99 to itsoriginal position to limit the return force of the piston and therebycontrol the suction force produced in chamber 90. By this means,cavitation on the suction side of the pump is regulated. Multiple checkvalves 96, 96.1, 96.6 and 96.7 regulate the flow and prevent back flowduring the pumping cycle.

The metering portion of assembly 81, as best shown in FIG. 6, consistsof pumps 94 and 94.1, which are coupled by a metering regulation arm 95.Metering pump 94.1 is

driven by a ball-bearing cam system 88.2 and a return spring member 93in a manner similar to pump and pump 94 is also driven by drive cam 88.2through regulation arm 95. Arm 95 is supported by fulcrum and kept incontact with cam 88.2 by spring 101. Pump 94 draws in the concentratedelectrolyte solution, and through its displacement is adjustable, itwill be set to displace about one-fortieth 4 the displacement of thepump 94.1. The two (2) metering pumps are mechanically locked togetherso that the fixed ratio of displacement is maintained, even if thevolume pumped should diminish due to suction pressure limitation asdescribed above.

As has also been pointed out, the pump assembly is designed to deliver apressure of about 600 to 700 p.s.i. and is limited to a suction pressure-5 p.s.i. The pumps 90 of the assembly draw approximately 21 ml. perminute of spent dialysate 16 from hemodialyzer 12, the patients heartproviding the pressure to force the blood into the hemodialyzer and backto return venous cannula 18. The micro-pumps 90 also supply spentdialysate to the hyperfiltration stage at a rate of about 21 mL/minute.The metering pump system is designed to handle up to the full 21 ml. perminute flow, hence it will always be able to pump the effiux from thefiltration stage and will always operate in the suction limit condition.This makes for stable operation of the entire high pressure micro-pumpmetering system.

Turning to FIG. 7, the relationship between pump chamber 90, input andoutput multiple check valves 96 and 96.7, and the ball-bearing camsystem can be seen more clearly. Spring member 92 provides the means forreturning piston 99 to its extreme upper position and prevents it fromfollowing the cam in the event that the suction pressure limit isexceeded, and by this means prevents cavitation. Diaphragm 91 ispermanently bonded to the base of chamber 90 and to piston 99, but isfree to move on its sides. The inlet and outlet ports may communicatewith the chamber 90 separately, or through a common channel 108, sincethe multiple check valves 96 and 96.7 control the directional movementof the fluid that is being pumped.

The pump is in operation continuously, hence we prefer a high efiiciencypump with a long fatigue life so as to permit a year or more oftrouble-free operation. As has been pointed out, 500 to 700 p.s.i. isthe preferable pressure output maximum to overcome osmotic backpressure. Furthermore,.pressures in the range of 500 to 700 p.s.i. areconsidered optimum from the standpoint of membrane life. A volume flowof 21 ml./ min. is provided for on the basis of purifying 30 liters ofdialysate per day. This figure of 30 liters/ day is chosen on the basisof engineering and design considerations as equivalent to desired rateof purification of the blood. Physiologically, a range of 20 to about 90liters of blood/day may be acceptable, the object being to remove fromabout 8 to about 24 grams/ day of urea, as a standard, from thebloodstream.

Generally, the hemodialyzer should permit diffusion of solutes ofmolecular weight less than 5,000 but can easily be constructedto passsolutes of higher molecular weights as high as 30,000. Blood channels inthe hemodialyzer should permit as high a flux as is consonant with lowpolarization, and with preservation of blood platelets and red cells.

One of the desirable features of this invention is the small amount ofvolume occupied by the make-up solution, which supplies about 200 to 300grams of solids/ day to the dialysate to replenish that removed by thehyperfilter as waste, and to maintain a concentration of electrolytes inthe dialysate equivalent to that in the blood to prevent their removalfrom the blood during dialysis. The make-up solution can have aconcentration of about 200 to 400 mg./ml.; hence, only one or two dailyloadings of the small (less than one liter) make-up reservoir arerequired. We prefer two loadings per day of about grams of solids in 300ml. of solution. Further, the

make-up solution is only added to the dialysate and is never mixed withthe patients blood, thus eliminating a potential source of contaminationof the blood from this solution.

Alternative embodiments of this invention can be understood by referringto FIGS. 1B, 1C, and 1D.

In the embodiment shown in FIG. 1B, the electrolytes in spent dialysate16 are first removed and then discarded with the low molecular weightsolutes as waste to reduce the load on hyperfilter 60.

With reference to FIG. 1B, spent dialysate 16 instead of being routeddirectly to hyperfilter 60 is first passed through a low-powerelectrodialyzer with membranes 2. The charge diiferential in theelectrodialyzer separates the electrolytes from the non-electrolytesolutes with the help of the membranes. The electrodialyzed, aqueoussolution 21 of primarily non-electrolyte solutes is then passed throughpump 81 and pumped into hyperfilter 60. The material 15 rejected by thehyperfilter is then returned to the electrodialyzer as theelectrodialysate for removal of the electrolytes from dialysate 16. As aresult of the electrodialysis treatment, the diflerence in concentrationof electrolytes between the filtrate side 6.9 of the hyperfilter and theretained solute side 6.5 is sharply reduced. Consequently, the wastematerial 25 deposited in the urinal in the instant embodiment can bemore highly con centrated in terms of waste products and electrolytesthan is the waste from the hyperfilter in the basic embodiment.

The osmotic pressure across the hyperfilter, which tends to force waterfrom 6.9 to 6.5 and solutes from 6.5 to 6.9 is correspondingly reduced.As a result, the pressure of the pump and hence the energy expended canbe reduced and less water is lost to waste 25. The power saved inpumping may be used by the electrodialysis unit to provide the chargeditferential.

In the basic embodiment described above, i.e., FIG. 1A, pressures in therange of 500 to 700 p.s.i. are required to force water through thehyperfilter. This is so partly because the cellulose acetate skinmembranes are tight enough to prevent the passage of small solutes andhence require a substantial pressure drop to force the water through.But a large contributing factor is the high os motic back pressure whichmust be overcome before water can pass from the concentrated side 6.5 tothe fresh water side 6.9. For a concentration ratio of six, for example,the back osmotic pressure of the concentrated side 6.5 would beapproximately 550 p.s.i. In the instant embodiment, the amount offiltrate 17 obtained can be increased without necessity of overcomingin-' creased osmotic pressure on the filtrate side 6.9 of thehyperfilter. Under these conditions, the rejected waste or urine 25 isconcentrated to the point where only two (2) liters of this waste areformed daily. It is to be understood that the higher rate of urineformation in the basic embodiment is not a serious disadvantage in thatthe patient, by drinking an average of less than a cup per hour, caneasily replace five (5) liters of fluid per day.

Referring to FIG. 1C, where still another embodiment of the invention isschematically outlined, it will be seen that the advantages of theembodiment of FIG. 1B are retained, while the electrolytes removed fromthe spent dialysate are utilized to reconstitute purified dialysate. Inthis embodiment, the electrodialyzed, aqueous solution 21 of primarilynon-electrolyte solutes is passed to hyperfilter 60 and the filtrate 17is returned to the electrodialysis treatment as the electrodialysaterather than the material rejected by the hyperfilter. After leaving theelectrodialyzer, instead of flowing to the urinal, as was the case inthe previous embodiment, the electrolytes in the purified filtrate 17flow to metering pump 93 for mixture, if any, with make-up electrolyteand are recycled to hemodialyzer 12 as reconstituted dialysate. Thewaste retained by the hyperfilter 15 is thus primarily urea,

10 creatinine, uric acid, sugars, and the like. The effiux 25 of theelectrodialyzer is free of toxic materials such as urea, and istherefore essentially suitable for reuse.

As in the embodiment shown in FIG. 1B, the osmotic pressure from thefiltrate side of hyperfilter 6.9 and the concentrated side 6.5 isreduced by removing the electrolytes in the electrodialyzer, and therate of urine production is again out back to about two (2) liters perday. Since the removed electrolytes are utilized in this embodiment, asmaller amount of make-up solution is required. A necessary function ofthe natural kidney is to remove a small amount of potassium from theblood. Hence, all of the electrolytes cannot be saved, because of thedifficulty of separating sodium and potassium ions, and thus with thepassing of a small amount of potassium to the urine, so also must pass asimilar proportion of sodium ion. It is, therefore, another feature ofthe instant embodiment to provide means for performing thiselectrolyte-adjustment function by partial removal of potassium ion. Theamount of make-up solution needed will be dependent upon the potassiumbalance. A reduction in the amount of electrolyte by approximatelyone-half /2) is feasible.

In FIG. 1D still another embodiment of the invention is schematicallyillustrated. In this embodiment, the filtering surface of thehyperfilter is a so-called mosaic membrane, which consists of tinypatches of cationic and anionic membranes allowing passage of ions ofboth polarities under concentration gradients. At the patch boundaries,lateral surface currents prevent the phenomenon known as electricpolarization. In any high filtration means, such as the hyperfilter ofthis invention, the concentration of solutes on the filtrate side 6.9will be very much lower than on the retention side 6.5, therebyproviding a substantial concentration gradient across the membrane. Thefiltrate 17 in the embodiment of FIG. 1D will contain electrolytes andpure water, while the rejected matter 15 will contain urea, creatinine,uric acid, and the like. It can readily be seen that the instantembodiment is nearly as sophisticated as a natural kidney. As a result,like the embodiment of FIG. 10, the required amount of make-upelectrolytes is considerably reduced. The complete hyperfilter wouldconsist of mosaic membranes in series with cellulose acetate membranesin order to permit controlled electrolyte passage into the hyperfilter.

It is within the scope of this invention to construct a non-wearableartificial kidney employing hemodialysis and hyperfiltration in themanner disclosed. It is also within the scope of this invention tomodify the nature of the power source. Any source of electric power,portable or non-portable, can be used with this invention.

Many other modifications in this invention are possible. Various motorand pump arrangements could be substituted without departing from thespirit and scope of the invention. Various modifications of themembranes used in the hemodialyzer and filter could be made. Forexample, a modification of this invention would be the inclusion ofso-called fail-safe features to protect against punctures, leaks, orruptures in the fluid lines of the system, as well as clogging of thefilter. Thus, it is within the scope of this invention to includevarious shut-down switches which are automatically activated bysignificant changes in flow or concentration at various points of thesystem. For example, a sensing switch can be incorporated in the systembetween the metering pumps and the hemodialyzer to measure the ionicconductivity of the reconstituted dialysate. In the event the meteringpumps or filters are malfunctioning and the dialysate has not beenadjusted to the proper electrolyte concentration, as determined by theionic conductivity of the materal, an automatic shut-oil switch for themotor will be actuated stopping the kidney and the removal of theseelectrolytes from the blood. Additionally, a similar sensing switch canbe incorporated in the system to measure the ionic conductivity of thewaste material in the urinal. Again, if excessive material is passingthrough the hyperfilter as waste, as determined by the ionicconductivity, an automatic shut-off will stop the motor, alerting thewearer of a malfunction and to a need for a maintenance check.

Various other design features may be incorporated, particularly withregard to the manner in which a compact artificial kidney of thisinvention is adapted to be worn on the body. For example, the urinal andelectrolyte make-up cannister may be adapted to fit comfortably onvarious parts of the body, such as the legs or hips. Other elements ofthe device may be adapted to be worn around the waist, build intoclothing or the like.

Still another modification of this invention is the inclusion ofdextrose or other non-electrolytes in a makeup reservoir connected tothe venous return so that the patient need not replace these materials'by oral ingestion. It is also within the scope of the invention to useanticoagulants, such as heparin or coumadin, in the artificial kidneysystem as an added safety factor with regard to possibility of clotting.

This invention in its broader aspects is not limited to the specificdetails shown and described, and departures may be made from suchdetails without departing from the principles of the invention andwithout sacrificing its chief advantages.

What is claimed is:

1. Apparatus for removing toxic substances from body fluids comprising:

(a) dialysis means containing a selective membrane for removing toxicsolutes from the body fluid;

(b) means for conveying the body fluid to one side of the membrane ofthe dialysis means;

(c) means for conveying a water-containing dialysate essentially free ofsaid toxic solutes to the other side of the membrane to establish asolute concentration gradient and to cause their diffusion across themembrane;

(d) dialysate purification means comprising a plurality of membraneswith hyperfiltration characteristics enclosed and supported in asuitable housing, said housing having influx means, purified aqueousfiltrate efllux means, and toxic solute efflux means for removing thetoxic solutes from said dialysate;

(e) means for conveying spent dialyste containing toxic solutes from thedialysis means to the dialysate purification means, said spent dialysateconveying means being constructed and arranged to permit theinterposition between the dialysis means and the dialysate purification,of a means for overcoming osmotic back pressure in the dialysatepurification means; and

(f) means for returning purified dialysate to the dialysis means.

2. The apparatus of claim 1, in which the influx means, the filtrateefliux means, and the toxic solute efllux means of said dialysatepurification means are so constructed and arranged that the flow fromthe influx means to the filtrate efflux is smooth and uninterrupted andis parallel to the filtering surfaces of the hypoperfiltrationmembranes.

3. The dialysate purification means of claim 2, in which thehyperfiltration membranes are planar.

4. The apparatus of claim 2, in which the hyperfiltration membranes aretubular.

5. The apparatus of claim 4, in which the tubular membranes have anoutside diameter of less than 1 mm.

6. The apparatus of claim 2, in which the plurality of hyperfiltrationmembranes comprise cellulose acetate.

7. The apparatus of claim 2, in which the filtering element comprises atleast one homogeneous membrane and at least one mosaic membrane, saidmosaic membrane comprising a patchwork of individual membrane segments.

8. The apparatus of claim 1, in which the dialysate purification meanscomprises:

an electrodialysis means having influx means for the spent dialysatefrom the dialysis means, efilux means for the non-electrolyte product ofelectrodialysis, a

second influx means, and a second efllux means;

a filtration means comprising a hyperfiltration element supported andenclosed in a suitable housing having influx means, filtrate efliuxmeans, and toxic solute efliux means;

the non-electrolyte elflux means of said electrodialysis means being incommunication with the means for overcoming osmotic back pressure, theinput means to said filtration means being in communication with themeans for overcoming osmotic pressure, the filtrate efflux means beingin communication with the means for returning purified dialysate to thedialysis means, the toxic solute efflux means being in communicationwith the second influx to the electrodialysis means such that the toxicsolutes conveyed thereto will mix with the aqueous electrolytes retainedby the electrodialysis means, and the second efliux means of theelectrodialysis means connected with means for discarding electrolytesand toxic solutes.

9. The apparatus of claim 1, in which the dialysate purification meanscomprises:

an electrodialysis means having influx means for the spent dialysatefrom dialysis means, efilux means for the non-electrolyte product ofelectrodialysis, a second influx means, and a second efiiux means;

a filtration comprising a hyperfiltration element enclosed and supportedin a suitable housing having influx means, filtrate efllux means, andefflux means for retained toxic solutes;

the non-electrolyte efilux means being connected by suitablecommunication means with the means for overcoming osmotic back pressure,and the means for overcoming osmotic back pressure being so arranged asto convey by suitable communication means the non-electrolyte product tothe filtration input means, the toxic solute efllux means being soconstructed and arranged as to permit the discarding of the toxicsolutes, the filtrate efilux means being in communication with thesecond influx means of the electrodialysis means, such that the filtrateconveyed thereto will mix with the aqueous electrolytes retained by theelectrodialysis means, and the second efilux means of theelectrodialysis means being in communication with the means forreturning purified dialysate to the dialysis means.

10. The apparatus of claim 1, in which the means for overcoming osmoticpressure comprises a cam-driven reciprocating pump with suction-limitingmeans.

11. The apparatus of claim 1, in which the dialysis means comprises aplurality of semi-permeable membranes so constructed and arranged thatthe flow of body fluid is smooth and uninterrupted and is parallel tothe surfaces of the membranes.

12. The dialysis means of claim 11, in which the membranes are planar.

13. The dialysis means of claim 11, in which the membranes are tubular.

14. The apparatus of claim 1, including:

a make-up electrolyte fluid reservoir, and means for 65 introducingsmall increments of said fluid from the reservoir into purified diaysatebeing returned to the dialysis means to maintain a level ofconcentration of electrolytes in the dialysate substantially equal tothe level of concentration of the electrolytes in the body fluid.

15. The apparatus of claim '14, in which the means for introducing themake-up electrolyte fluid comprises a metering pump, the pumps inputscommunicating with 75 the make-up electrolyte. fluid reservoir and thedialysate 13 purification means and its outputs with means for combiningthe outputs as reconstituted dialysate.

16. The apparatus of claim 15, in which the metering pump ismechanically linked to the means for overcoming osmotic back pressure inthe dialysate purification means, the means for overcoming osmotic backpressure comprising a pump with a greater displacement than the meteringpump.

17. The apparatus of claim 14, in which the make-up electrolyte fluidreservoir contains less than 300 grams of solids dissolved in less than1 liter of water.

18. An artificial kidney comprising:

an arterial cannula;

hemodialysis means containing semi-permeable membranes for removingtoxic solutes from the blood;

a first conduit means providing communication between the arterialcannula and the membranes, said conduit means being so arranged that thearterial blood flows smoothly and uninterruptedly over one surface ofthe membranes;

a second conduit means providing communication of a water-containingdialysate essentially free of said toxic solutes to the hemodalysismeans, said second conduit means being arranged so that the dialysateflows smoothly and uninterruptedly over the opposite surface of themembranes from and countercurrent to the flow of blood, a third conduitmeans providing communication of spent dialystate containing the toxicsolutes from the hemodialysis means to a highpressure pump;

a filtration element permeable to pure water but essentially impermeableto the toxic solutes;

a fourth conduit means providing communication between the high-pressurepump and the filtration element;

means for introducing, at a predetermined rate, increments of an aqueoussolution of electrolytes into the filtrate flowing from the filtrationelement;

said second conduit means conveying the resulting mixture of saidfiltrate and said electrolyte solution as reconstituted dialysate to thehemodialysis means; and

means for conveying the resulting purified blood residue from thehemodialysis means to a venous cannula.

19. The apparatus of claim 18, in which the hemodialysis means comprisesa stack of rectangular membrane sheets spaced by rows of filamentsparallel to each other and to the edges of the sheets, each pair ofspaced membrane sheets being separated from the pair immediately aboveand the pair immediately below by sheets of porous support materialdisposed parallel to and contiguous with the surfaces of the membranesheets.

20. A method of removing toxic substances from the blood comprising:

subjecting arterial blood to hemodialysis utilizing a semi-permeablemembrane and a dialysate essentially 14 free of toxic substances in theblood, such that the toxic solids diffuse through the membrane into thedialysate, filtering the spent dialysate containing the toxic solutes toremove them from the dialysate, mixing filtered dialystate with acontrolled amount of make-up electrolyte solution and recycling themixture of filtered dialysate and electrolytes for further use duringhemodialysis.

21. The method of claim 20, in which electrodialysis is used incombination with the filtration, such that osmotic back pressure fromthe purified dialysate filtrate to the retained toxic solutes isreduced.

22. The method of claim 21, in which selective electrodialysis is usedto recover electrolytes from the spent dialysate, and these electrolytesare then added to the purified dialysate filtrate.

23. A method of removing toxic substances from peritoneal fluid,comprising:

subjecting the peritoneal fluid to peritoneal dialysis utilizing asemi-permeable membrane and a dialysate essentially free of toxicsubstances in the peritoneal fluid, such that the toxic solids diflusethrough the membrane into the dialysate, filtering the spent dialysatecontaining the toxic solutes to remove them from the dialysate, mixingfiltered dialysate with the controlled amount of make-up electrolytessolution and recycling the filter dialystate and electrolytes forfurther use during dialysis.

24. The method of claim 23, in which electrodialysis is used incombination with the filtration, such that osmotic back pressure fromthe purified dialysate filtrate to the retained toxic solutes isreduced.

25. The method of claim 24, in which selective electrodialysis is usedto recover electrolytes from the spent dialysate and these electrolyteshave been added to the purified dialysate filtrate.

References Cited UNITED STATES PATENTS 3,506,126 4/1970 Serfass et al210-259 X 3,401,798 9/1968 Hyrop 210321 3,228,876 1/1966 Mahon 2l0223,268,441 8/1966 Lindstrom 2l022 3,483,867 12/1969 Markovitz 21023 X3,630,378 12/1971 Bauman 210-321 X 3,579,441 5/1971 Brown 210-233,498,909 3/ 1970 Littman 21023 FRANK A. SPEAR, 111., Primary ExaminerUS. Cl. X.R. 21023, 321

Patent No. 3,7995% Bated March 26, 1974 Inventofls) Y .CllfiLi-JQ bi-ownIt is cer'tif ier that error eppee s in the above-identified patent andthat said Letters Patent are here corrected as shown below:

Column 11, line 61, change "hypoprfil to hyperfil- Column 12, line .23,before "connected" insert being line 31, before "comprising" insertmeans Signed and sealed 10th day of September 197%;

Attest:

MCCGY Me GIBSON, MARSHALL DANN lattes-sing Gfficer Commissioner ofPatents FORM PC4650 H069) uscoMM-Dc 60376-P69 U. 5. GOVERNMENT PRXNTINGOFFICE 1969 0-366-334,

